Green tea polyphenol epigallocatechin-3-gallate enhances 5-fluorouracil-induced cell growth inhibition of hepatocellular carcinoma cells.

Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Guangzhou Medical University Department of Ophthalmology, Guangzhou No. 8 People's Hospital, Guangzhou, China.
Hepatology Research (Impact Factor: 2.22). 01/2012; 42(5):494-501. DOI: 10.1111/j.1872-034X.2011.00947.x
Source: PubMed

ABSTRACT Aim:  5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic drugs. Resistance to 5-FU is a major cause of chemotherapy failure in advanced-stage hepatocellular carcinoma (HCC). Green tea polyphenol Epigallocatechin-3-gallate (EGCG) plays a critical role in growth inhibition and apoptotic induction in HCC cell lines. The aim of this study is to investigate whether EGCG can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms. Methods:  3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cell growth. Western blotting analysis was performed to detect the proteins expression in Hep3B cells. Small interfering RNA was used to suppress cyclooxygenase-2 (COX-2) expression. Furthermore, enzyme linked immunosorbent assay was used to test the prostaglandin E(2) (PGE(2) ) production in cell cultures. Results:  Epigallocatechin-3-gallate augmented the anti-tumor effect of 5-FU in Hep3B cells. Significant difference was observed between the treated groups and the control group (P < 0.05). EGCG (its concentrations at over 5 µmol/L) combined with 5-FU presented a synergic effect. Furthermore, the combination of EGCG and 5-FU abrogated the COX-2 overexpression and PGE(2) secretion induced by 5-FU. The upregulation of COX-2 expression decreased the phosphorylation of Akt (Thr(308) ) expression. These appeared to be followed by the AMPK hyperactivation. Conclusion:  Epigallocatechin-3-gallate sensitizes HCC cells to 5-FU antitumor activity, and the combination of EGCG and 5-FU exhibits synergism in chemo-resistant cancer cells. The results suggest potential novel therapies for the treatment of advanced-stage liver cancer.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is the third most common type of cancer worldwide, causing over 370 000 deaths per year, with approximately half of them in China. Chemotherapy is the optimal treatment for patients with advanced HCC, although chemoresistance has become a significant obstacle to successful liver cancer surgery. In this paper, we have assessed the characteristics of drugs to explore the effects of individual and combined action of organic silicone quaternary ammonium salt (Jieyoushen) and 5-fluorouracil (5-FU). The results of MTT assays showed that single and combined action of Jieyoushen and 5-FU can inhibit the proliferation of liver carcinoma cell lines in a dose-dependent and time-dependent manner, respectively. Electron microscopy and Hoechst 33342 staining showed characteristic apoptotic bodies in apoptotic cells treated with Jieyoushen and 5-FU. Flow cytometry results indicated that the percentage of cells at G0/G1 phase gradually increased, whereas it gradually decreased during the S phase after treatment. Taken together, these results suggest that the combination of Jieyoushen with 5-FU exerts a synergistic anticancer effect on HCC growth and that targeted therapeutic strategies may improve HCC sensitivity to chemotherapy.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 09/2014; 23(5):372-84. DOI:10.1097/CEJ.0b013e328364f2c8 · 2.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: (-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to inhibit cell proliferation and induce apoptosis in several types of human tumors. The most common site of distant metastases in colorectal cancer is the liver. However, no previous studies have reported the ability of EGCG to suppress liver metastases of human colorectal cancer. The aim of the present study was to elucidate the potential use of EGCG as chemotherapy targeting liver metastases of human colorectal cancer. To assess the effect of EGCG on human colorectal cancer cell lines, RKO and HCT116, cell viability, cell proliferation and apoptosis were measured by cell counting kit-8, BrdU assay and TUNEL staining, respectively. Protein and gene expression were measured by western blot analysis and RT-PCR analysis, respectively. EGCG inhibited cell proliferation and induced apoptosis. EGCG dephosphorylated constitutively activated Akt and increased the activation of p38. EGCG also decreased the expression of vascular endothelial growth factor receptor 2. Additionally, the ability of EGCG to prevent the development of liver metastases of RKO tumors was evaluated in SCID mice. EGCG suppressed angiogenesis and induced apoptosis in liver metastases without associated body weight loss or hepatotoxicity. Furthermore, the liver metastatic area was significantly reduced by EGCG administration. Our findings indicate that EGCG may be useful in the treatment of liver metastases of human colorectal cancer.
    Oncology Reports 12/2013; 31(2). DOI:10.3892/or.2013.2925 · 2.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.
    Korean Journal of Physiology and Pharmacology 02/2014; 18(1):61-6. DOI:10.4196/kjpp.2014.18.1.61 · 1.26 Impact Factor